FDA lays down the law on gene ther­a­py, of­fer­ing guid­ances on both dis­eases and pro­ce­dures

Zachary Brennan

As first an­nounced in Jan­u­ary, the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) on Wednes­day of­fered a swath of new draft guid­ance doc­u­ments on hu­man gene ther­a­pies — of­fer­ing a look at what it ex­pects from an in­dus­try that’s be­gin­ning to take off.

The six guid­ance doc­u­ments fo­cus on de­vel­op­ing he­mo­phil­ia, rare dis­ease and reti­nal dis­or­der gene ther­a­pies, and in­clude one on chem­istry, man­u­fac­tur­ing and con­trol (CMC) in­for­ma­tion, one on long term fol­low-up ob­ser­va­tion­al stud­ies col­lect­ing da­ta on ad­verse events and one on the test­ing of retro­vi­ral vec­tor-based ther­a­pies.

Last De­cem­ber, the FDA ap­proved a new gene ther­a­py, priced at $850,000, from Spark Ther­a­peu­tics for the treat­ment of chil­dren and adult pa­tients with an in­her­it­ed form of vi­sion loss that may re­sult in blind­ness. And back in 2016, FDA be­gan to see the num­ber of gene and cell ther­a­py ap­pli­ca­tions spike.

Last No­vem­ber, the FDA al­so an­nounced its pol­i­cy frame­work for re­gen­er­a­tive med­i­cine, in­clud­ing a draft guid­ance that de­scribes the ex­pe­dit­ed pro­grams, such as the break­through ther­a­py des­ig­na­tion, and the re­gen­er­a­tive med­i­cine ad­vanced ther­a­py (RMAT) des­ig­na­tion, that may be avail­able to spon­sors of these ther­a­pies. Com­pa­nies have al­ready weighed in on such guid­ance.

The draft guid­ance al­so in­cludes rec­om­men­da­tions re­gard­ing pre­clin­i­cal and clin­i­cal con­sid­er­a­tions to sup­port de­vel­op­ment of he­mo­phil­ia gene ther­a­pies (GTs), as well as in­for­ma­tion on ex­pe­dit­ed pro­grams and com­mu­ni­ca­tion with the FDA.

This 14-page draft guid­ance pro­vides rec­om­men­da­tions on de­vel­op­ing a GT prod­uct in­tend­ed to treat a rare dis­ease in adult and/or pe­di­atric pa­tients. The guid­ance re­lates to the man­u­fac­tur­ing, pre­clin­i­cal, and clin­i­cal tri­al de­sign is­sues for all phas­es of the clin­i­cal de­vel­op­ment pro­gram.

“Such in­for­ma­tion is in­tend­ed to as­sist spon­sors in de­sign­ing clin­i­cal de­vel­op­ment pro­grams for such prod­ucts, where there may be lim­it­ed study pop­u­la­tion size and po­ten­tial fea­si­bil­i­ty and safe­ty is­sues as well as is­sues re­lat­ing to the in­ter­pretabil­i­ty of bioac­tiv­i­ty/ef­fi­ca­cy out­comes that may be unique to rare dis­eases or to the na­ture of the GT prod­uct it­self,” the FDA said.

The draft ap­plies to GTs and to com­bi­na­tion prod­ucts that con­tain a hu­man gene ther­a­py in com­bi­na­tion with a drug or de­vice.

“The field of gene ther­a­py has pro­gressed rapid­ly since FDA is­sued the April 2008 guid­ance. There­fore, FDA is up­dat­ing the guid­ance to pro­vide cur­rent FDA rec­om­men­da­tions re­gard­ing the CMC con­tent of a gene ther­a­py IND,” the FDA said.

When fi­nal­ized, the draft is in­tend­ed to su­per­sede the doc­u­ment en­ti­tled “Guid­ance for FDA Re­view­ers and Spon­sors: Con­tent and Re­view of Chem­istry, Man­u­fac­tur­ing, and Con­trol (CMC) In­for­ma­tion for Hu­man Gene Ther­a­py In­ves­ti­ga­tion­al New Drug Ap­pli­ca­tions (INDs),” from April 2008.

This 36-page draft guid­ance pro­vides spon­sors with rec­om­men­da­tions re­gard­ing the de­sign of pro­to­cols for long term fol­low-up ob­ser­va­tion­al stud­ies for the col­lec­tion of da­ta on de­layed ad­verse events fol­low­ing the ad­min­is­tra­tion of a GT.

When fi­nal­ized, the draft is in­tend­ed to su­per­sede the doc­u­ment en­ti­tled “Guid­ance for In­dus­try: Gene Ther­a­py Clin­i­cal Tri­als–Ob­serv­ing Par­tic­i­pants for De­layed Ad­verse Events” from No­vem­ber 2006. This draft, when fi­nal­ized, is al­so in­tend­ed to sup­ple­ment the guid­ance dis­cussed be­low.

“Rec­om­men­da­tions in­clude the iden­ti­fi­ca­tion and amount of ma­te­r­i­al to be test­ed, and gen­er­al test­ing meth­ods,” the FDA said. “In ad­di­tion, rec­om­men­da­tions are pro­vid­ed on mon­i­tor­ing pa­tients for ev­i­dence of retro­vi­ral in­fec­tion af­ter ad­min­is­tra­tion of retro­vi­ral vec­tor-based gene ther­a­py prod­ucts.”

When fi­nal­ized, the draft is in­tend­ed to su­per­sede the doc­u­ment en­ti­tled “Guid­ance for In­dus­try: Sup­ple­men­tal Guid­ance on Test­ing for Repli­ca­tion Com­pe­tent Retro­virus in Retro­vi­ral Vec­tor Based Gene Ther­a­py Prod­ucts and Dur­ing Fol­low-up of Pa­tients in Clin­i­cal Tri­als Us­ing Retro­vi­ral Vec­tors,” from No­vem­ber 2006.

The draft guid­ance, when fi­nal­ized, is al­so in­tend­ed to sup­ple­ment the long term fol­low-up and CMC guid­ance doc­u­ments dis­cussed above.

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

Jason Mast

Associate Editor

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

John Carroll

Editor & Founder

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

Natalie Grover

Reporter

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Recursion Pharmaceuticals

Salt Lake City, UT

John Carroll

Editor & Founder

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Natalie Grover

Reporter

Amber Tong

Editor

Jason Mast

Associate Editor

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communicationslast month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

John Carroll

Editor & Founder

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

Natalie Grover

Reporter

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

New York, NY

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Natalie Grover

Reporter

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Endpoints Staff

→ Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

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